DESCRIPTION (taken from the application): Although 14% of the United States population suffers from chronic musculoskeletal pain, most of our knowledge about pain has been obtained from studies on cutaneous pain. The current models of musculoskeletal pain typically produce short term hyperalgesia (resolved in 24 h or less). However, clinically, chronic muscle pain, as experienced by people with fibromyalgia, is long lasting (months to years). In preliminary studies, I determined that a long lasting bilateral hyperalgesia can be induced by two injections of low pH saline, five days apart, into one gastrocnemius muscle. In the work proposed I hypothesize that the development of the long lasting bilateral hyperalgesia is dependent initially on input from the site of injection following both the first and second injection. I further propose that once the long lasting hyperalgesia develops plastic changes in the central nervous system occur that maintain the hyperalgesia through increased activity in spinal neurons. The specific aims will establish and characterize a new model of muscle pain that is chronic and widespread. The proposed studies will establish if the neural mechanisms involved in the development and maintenance of chronic pain, induced by stimulation of muscle nociceptors, involve peripheral or central nervous system processes. These proposed studies will help in the understanding and thus potential treatment of chronic muscle pain, including such conditions as fibromyalgia, myofascial pain and low back pain.